OP0146 ISOLATED ANTI-Ro52 ANTIBODIES IN SJÖGREN’S SYNDROME: A MILDER INFLAMMATORY PHENOTYPE AT HIGHER RISK FOR FIBROTIC ORGAN INVOLVEMENT
Authors: S. Fonzetti, F. Ferro, G. La Rocca, G. Fulvio, I. C. Navarro García, G. Governato, V. Donati, M. Mosca, C. Baldini
Journal: Annals of the Rheumatic Diseases (2022)

Background Autoimmune response against the Ro antigen (Ro52 and/or Ro60 subunits) represents a distinctive serological hallmark in primary Sjögren Syndrome (pSS). The double positivity for anti-Ro60 and anti-Ro52 has been associated with a higher glandular inflammation and B-cell hyperactivity. By contrast, the clinical significance of isolated anti-Ro52 antibodies in pSS remains controversial. Objectives To investigate the association between isolated anti-Ro52 antibodies and glandular and extra-glandular pSS features in order to explore whether anti-Ro52 antibodies may help to identify a specific subset of pSS. Methods In this retrospective study we included unselected pSS patients prospectively followed at our Unit between 2012 to 2021. Of them, anti-Ro/SSA positive patients were identified and stratified by the presence of anti-Ro52 isolated, anti-Ro60 isolated and both anti-Ro60 and anti-Ro52. Demographics, clinical, biological and histological data were compared between the three groups. Data were presented as mean±SD, or percent frequency as appropriate. Intergroup comparisons were made using the t-test/Mann–Whitney test for continuous variables and Fisher’s exact test for categorical variables. Results Out of a study cohort of 432 pSS patients, we included 300 anti-Ro/SSA positive patients (21 M: 279 F, mean age 57±14 yrs) followed for a mean follow-up of 6.5±6.7 years. Of them, 59/300 (19.7%) presented isolated Ro52 antibodies, 214/300 (71.3 %) both anti-Ro60 and anti-Ro52 and 27/300 (9%) had isolated Ro60 antibodies. At diagnosis, patients with anti-Ro52 alone were older than those with double positivity (57.4±13.2 vs 48.8±13.8, p=0.0001) and presented a lower focus score (FS) in their minor salivary gland biopsies (MSGBs) (p=0.9±1.0 vs 1.6±0.9, p=0.02). No differences in demographic and glandular infiltrate were detected between anti-Ro52 alone and anti-Ro60 alone patients. Similarly, the three subgroups did not differ in oral and ocular function tests as well as in the patient reported outcomes (ESSPRI, OHIP and OSDI). Salivary gland ultrasonography showed a decreasing trend of the OMERACT scoring system with the highest grade detected more commonly in anti-Ro60 and anti-Ro52 patients and the lowest grade in anti-Ro60 alone. Regarding extraglandular manifestations significant differences were observed among the three subgroups as shown in the heat map (Figure 1). Patients with anti-Ro52 alone presented the highest frequency of interstitial lung disease (ILD) and primary biliary cirrhosis (PBC) and the lowest prevalence of lymphadenopathy, anti-La/SSB and hyper-IgG (p&lt;0.05). By contrast, patients presenting anti-Ro52 in association with anti-Ro60 had a prominent B cell hyperactivity with higher levels of serum IgG, anti-La SSB antibodies and Rheumatoid factor positivity (p&lt;0.05). Finally, patients with isolated anti-Ro60 presented a milder disease activity and an ESSDAI (3.4±4.5 vs 6.3±4.8 vs 5.2±5.1, p=0.009) significantly lower than the other two subgroups. Conclusion Patients with isolated anti-Ro52 seems to represent a specific subset of pSS with milder tissue focal inflammation but at higher risk for systemic fibrotic changes, particularly in the lungs. The identification of molecular pathogenetic processes, common to both isolated anti-Ro52 pSS and other anti-Ro52 positive connective tissue diseases may offer new insights into our understanding of disease etiology, and facilitate the development of targeted therapeutic approaches. Disclosure of Interests None declared